Heterodimerization of apelin receptor and neurotensin receptor 1 induces phosphorylation of ERK1/2 and cell proliferation via Gαq-mediated mechanism

Dimerization of G protein-coupled receptors (GPCRs) is crucial for receptor function including agonist affinity, efficacy, trafficking and specificity of signal transduction, including G protein coupling. Emerging data suggest that the cardiovascular system is the main target of apelin, which exerts an overall neuroprotective role, and is a positive regulator of angiotensin-converting enzyme 2 (ACE2) in heart failure. Moreover, ACE2 cleaves off C-terminal residues of vasoactive peptides including apelin-13, and neurotensin that activate the apelin receptor (APJ) and neurotensin receptor 1 (NTSR1) respectively, that belong to the A class of GPCRs. Therefore, based on the similar mode of modification by ACE2 at peptide level, the homology at amino acid level and the capability of forming dimers with other GPCRs, we have been suggested that APJ and NTSR1 can form a functional heterodimer. Using co-immunoprecipitation, BRET and FRET, we provided conclusive evidence of heterodimerization between APJ and NTSR1 in a constitutive and induced form. Upon agonist stimulation, hetrodimerization enhanced ERK1/2 activation and increased proliferation via activation of Gq α-subunits. These novel data provide evidence for a physiological role of APJ/NTSR1 heterodimers in terms of ERK1/2 activation and increased intracellular calcium and induced cell proliferation and provide potential new pharmaceutical targets for cardiovascular disease. © 2014 The Authors

NHL pathological image classification based on hierarchical local information and GoogLeNet-based representations

Background. Accurate classification for different non-Hodgkin lymphomas (NHL) is one of the main challenges in clinical pathological diagnosis due to its intrinsic complexity. Therefore, this paper proposes an effective classification model for three types of NHL pathological images, including mantle cell lymphoma (MCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Methods. There are three main parts with respect to our model. First, NHL pathological images stained by hematoxylin and eosin (H&E) are transferred into blue ratio (BR) and Lab spaces, respectively. Then specific patch-level textural and statistical features are extracted from BR images and color features are obtained from Lab images both using a hierarchical way, yielding a set of hand-crafted representations corresponding to different image spaces. A random forest classifier is subsequently trained for patch-level classification. Second, H&E images are cropped and fed into a pretrained google inception net (GoogLeNet) for learning high-level representations and a softmax classifier is used for patch-level classification. Finally, three image-level classification strategies based on patch-level results are discussed including a novel method for calculating the weighted sum of patch results. Different classification results are fused at both feature 1 and image levels to obtain a more satisfactory result. Results. The proposed model is evaluated on a public IICBU Malignant Lymphoma Dataset and achieves an improved overall accuracy of 0.991 and area under the receiver operating characteristic curve of 0.998. Conclusion. The experimentations demonstrate the significantly increased classification performance of the proposed model, indicating that it is a suitable classification approach for NHL pathological images

Existence of positive solutions for singular higher-order fractional differential equations with infinite-point boundary conditions

In this paper, we consider a class of singular fractional differential equations with infinite-point boundary conditions. The fractional orders are involved in the nonlinearity of the boundary value problem, and the nonlinearity is allowed to be singular with respect to not only the time variable but also to the space variable. Firstly, we give Green’s function and establish its properties. Then, we utilize the sequential technique and regularization to investigate the existence of positive solutions. Finally, we give an example of application of our result

Present-day Geostress Characteristics of the Central Region of the 1605 Qiongshan M 7.5 Earthquake and their Implications for Regional Fault Activity

Continuous subsidence, which has occurred over more than 100 km2 of the Dongzhai Harbor area, northeast Hainan Island, is likely to be associated with tectonic movement arising from the 1605 Qiongshan M 7.5 earthquake. It is the only earthquake in the history of China to have caused large-scale land subsidence into the sea, and the disaster led to the sinking of 72 villages. To understand the dynamic environment of this subsidence, a 300-meter-deep borehole was established on the eastern side of the Puqian town on the east coast of Dongzhai Harbor. A series of 10 in-situ stress measurements and 4 impression orientation measurements were carried out by the hydraulic fracturing method in the borehole. The results show that the maximum horizontal principal stress, SH, is between 5.70 to 12.07 MPa, and the minimum horizontal principal stress, Sh, is between 4.13 to 8.16 MPa. Compared with the magnitude of in-situ stress in the South China coastal area, the magnitude of the in-situ stress for Dongzhai Harbor is considered to be of a medium to upper level. The maximum horizontal principal stress direction is in the northwest direction (33.96°NW). The maximum and minimum horizontal lateral pressure coefficient values are both greater than 1, which indicates that the stress field at the measured point is mainly horizontal, with the principal stress increasing with the depth. The NW-trending principal compressive stress is likely to be one of the dynamic sources of the activity of the Puqian - Qinglan fault and the subsidence of the Dongzhai Harbor graben

Computational fluid dynamics investigation of thermal-hydraulic characteristics in a simplified pebbled bed modular reactor core using different arrangements of fuel elements

High-temperature gas-cooled reactor is a kind of advanced nuclear reactor in which the core is packed with spherical fuel elements. In high-temperature gas-cooled reactors, the operating temperature is higher than that in ordinary light water reactors. In an attempt to analyze the flow pattern and heat transfer situation to provide reference for the safe operation of the pebble bed reactors, a segment of simplified high-temperature gas-cooled reactor core is simulated with computational fluid dynamics method. Four kinds of arrangement, including simple cubic, body-centered cubic, face-centered cubic, and a combination structure of body-centered cubic and face-centered cubic, are studied, respectively. Based on the simulation results, higher heat transfer capability and lower pebble temperature are obtained in the case with the most compact arrangement. The drag coefficient (Cd) for four arrangements with different inlet Reynolds number (Re) is obtained and relationship between Re and Cd is analyzed. In addition, a simulation with a broken fuel element in the body-centered cubic fluid domain has been performed. The results show that the presence of broken fuel may result in uneven flow, which will change the heat transfer condition. So it is better to avoid broken fuel element in a high-temperature gas-cooled reactor

The 13N(d,n)14O Reaction and the Astrophysical 13N(p,g)14O Reaction Rate

$^{13}$N($p,\gamma$)$^{14}$O is one of the key reactions in the hot CNO cycle which occurs at stellar temperatures around $T_9$ $\geq$ 0.1. Up to now, some uncertainties still exist for the direct capture component in this reaction, thus an independent measurement is of importance. In present work, the angular distribution of the $^{13}$N($d,n$)$^{14}$O reaction at $E_{\rm{c.m.}}$ = 8.9 MeV has been measured in inverse kinematics, for the first time. Based on the distorted wave Born approximation (DWBA) analysis, the nuclear asymptotic normalization coefficient (ANC), $C^{^{14}O}_{1,1/2}$, for the ground state of $^{14}$O $\to$ $^{13}$N + $p$ is derived to be $5.42 \pm 0.48$ fm$^{-1/2}$. The $^{13}$N($p,\gamma$)$^{14}$O reaction is analyzed with the R-matrix approach, its astrophysical S-factors and reaction rates at energies of astrophysical relevance are then determined with the ANC. The implications of the present reaction rates on the evolution of novae are then discussed with the reaction network calculations.Comment: 17 pages and 8 figure

Direct Measurements of the Branching Fractions for Inclusive K±K^\pm and Inclusive Semileptonic Decays of D+D^+ and D0D^0 Mesons

With singly-tagged $\bar D$ samples selected from the data collected at and around 3.773 GeV with the BESII detector at the BEPC collider, we have measured the branching fractions for the inclusive $K^\pm$ decays of $D^+$ and $D^0$ mesons, which are $BF(D^+\to K^-X) = (24.7 \pm 1.3 \pm 1.2)$, $BF(D^+\to K^+X) = (6.1 \pm 0.9 \pm 0.4)$, $BF(D^0\to K^-X) = (57.8 \pm 1.6 \pm 3.2)$ and $BF(D^0\to K^+X) = (3.5 \pm 0.7 \pm 0.3)$, respectively. We have also measured the branching fractions for the inclusive semileptonic decays of $D^+$ and $D^0$ mesons to be $BF(D^+ \to e^+ X)=(15.2 \pm 0.9 \pm 0.8)$ and $BF(D^0 \to e^+ X) =(6.3 \pm 0.7 \pm 0.4)$. These yield the ratio of their partial widths to be $\Gamma(D^+ \to e^+X)/\Gamma(D^0 \to e^+X)=0.95 \pm 0.12 \pm 0.07$.Comment: 6 pages, 5 figure

Measurements of branching fractions for inclusive K0~/K0 and K*(892)+- decays of neutral and charged D mesons

Using the data sample of about 33 pb-1 collected at and around 3.773 GeV with the BES-II detector at the BEPC collider, we have studied inclusive K0~/K0 and K*(892)+- decays of D0 and D+ mesons. The branching fractions for the inclusive K0~/K0 and K*(892)- decays are measured to be BF(D0 to K0~/K0 X)=(47.6+-4.8+-3.0)%, BF(D+ to K0~/K0 X)=(60.5+-5.5+-3.3)%, BF(D0 to K*- X)=(15.3+- 8.3+- 1.9)% and BF(D+ to K*- X)=(5.7+- 5.2+- 0.7)%. The upper limits of the branching fractions for the inclusive K*(892)+ decays are set to be BF(D0 to K*+ X)<3.6% and BF(D+ to K*+ X) <20.3% at 90% confidence level